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Abstract
Thyroid hormones (TH) are endogenous compounds critical to mammalian metabolic regulation. Perfluoroalkyl substances (PFASs) are a group of xenobiotics known to influence the systemic concentration on THs in vivo, however their mechanism in not completely elucidated. The purpose of this work was to investigate the impact of two widely distributed PFAS compounds, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), on TH uptake as a potential mechanism of TH disruption. Using cryopreserved rat hepatocytes, we demonstrate that PFOA and PFOS are able to increase uptake of the TH, thyroxine (T4), as a consequence of competitive displacement from the serum binding protein transthyretin. To further assess the impact of hepatic transporters on T4 uptake, we evaluated T4 transport in liver specific organic anion transporting polypeptides (OATPs). Interestingly, transport of T4 was demonstrated in rat Oatp1b2 but not in human OATP1B1. Overall these findings provide a mechanism by which PFAS compounds may facilitate a decrease in systemic TH concentrations in vivo.